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Chronic Kidney Disease and Fibrosis: The Role of Uremic Retention Solutes.

Mutsaers HA, Stribos EG, Glorieux G, Vanholder R, Olinga P - Front Med (Lausanne) (2015)

Bottom Line: Chronic kidney disease (CKD) is a major global health concern, and the uremic state is highly associated with fibrogenesis in several organs and tissues.Another key feature of CKD is the retention and subsequent accumulation of solutes that are normally cleared by the healthy kidney.The purpose of this brief review is to gather and discuss the current body of evidence linking uremic retention solutes to the fibrotic response during CKD, with a special emphasis on the pathophysiological mechanisms in the kidney.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen , Groningen , Netherlands.

ABSTRACT
Chronic kidney disease (CKD) is a major global health concern, and the uremic state is highly associated with fibrogenesis in several organs and tissues. Fibrosis is characterized by excessive production and deposition of extracellular matrix proteins with a detrimental impact on organ function. Another key feature of CKD is the retention and subsequent accumulation of solutes that are normally cleared by the healthy kidney. Several of these uremic retention solutes, including indoxyl sulfate and p-cresyl sulfate, have been suggested to be CKD-specific triggers for the development and perpetuation of fibrosis. The purpose of this brief review is to gather and discuss the current body of evidence linking uremic retention solutes to the fibrotic response during CKD, with a special emphasis on the pathophysiological mechanisms in the kidney.

No MeSH data available.


Related in: MedlinePlus

The profibrotic effects of indoxyl sulfate. Schematic presentation of the pathophysiological mechanisms via which indoxyl sulfate promotes fibrogenesis in renal cells. Furthermore, similar effects have been described for other protein-bound uremic retention solutes, e.g., p-cresyl sulfate. See text for details. Chemical structure obtained from the Human Metabolome Database (www.hmdb.ca). α-SMA, α-smooth muscle actin; EMT, epithelial-to-mesenchymal transition; PAI-1, plasminogen activator inhibitor-1; COL1A1, alpha-1 type I collagen; ROS, reactive oxygen species; TGF-β, Transforming growth factor-β; TIMP-1, tissue inhibitor of metalloproteinases-1.
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Figure 1: The profibrotic effects of indoxyl sulfate. Schematic presentation of the pathophysiological mechanisms via which indoxyl sulfate promotes fibrogenesis in renal cells. Furthermore, similar effects have been described for other protein-bound uremic retention solutes, e.g., p-cresyl sulfate. See text for details. Chemical structure obtained from the Human Metabolome Database (www.hmdb.ca). α-SMA, α-smooth muscle actin; EMT, epithelial-to-mesenchymal transition; PAI-1, plasminogen activator inhibitor-1; COL1A1, alpha-1 type I collagen; ROS, reactive oxygen species; TGF-β, Transforming growth factor-β; TIMP-1, tissue inhibitor of metalloproteinases-1.

Mentions: Taken together, it is evident that indoxyl sulfate can contribute to renal fibrogenesis via an array of pathophysiological mechanisms (Figure 1), e.g., ROS production, stimulating expression of the profibrotic factor TGF-β, induction of EMT/EPC, promoting cellular senescence and by reducing klotho expression.


Chronic Kidney Disease and Fibrosis: The Role of Uremic Retention Solutes.

Mutsaers HA, Stribos EG, Glorieux G, Vanholder R, Olinga P - Front Med (Lausanne) (2015)

The profibrotic effects of indoxyl sulfate. Schematic presentation of the pathophysiological mechanisms via which indoxyl sulfate promotes fibrogenesis in renal cells. Furthermore, similar effects have been described for other protein-bound uremic retention solutes, e.g., p-cresyl sulfate. See text for details. Chemical structure obtained from the Human Metabolome Database (www.hmdb.ca). α-SMA, α-smooth muscle actin; EMT, epithelial-to-mesenchymal transition; PAI-1, plasminogen activator inhibitor-1; COL1A1, alpha-1 type I collagen; ROS, reactive oxygen species; TGF-β, Transforming growth factor-β; TIMP-1, tissue inhibitor of metalloproteinases-1.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4553389&req=5

Figure 1: The profibrotic effects of indoxyl sulfate. Schematic presentation of the pathophysiological mechanisms via which indoxyl sulfate promotes fibrogenesis in renal cells. Furthermore, similar effects have been described for other protein-bound uremic retention solutes, e.g., p-cresyl sulfate. See text for details. Chemical structure obtained from the Human Metabolome Database (www.hmdb.ca). α-SMA, α-smooth muscle actin; EMT, epithelial-to-mesenchymal transition; PAI-1, plasminogen activator inhibitor-1; COL1A1, alpha-1 type I collagen; ROS, reactive oxygen species; TGF-β, Transforming growth factor-β; TIMP-1, tissue inhibitor of metalloproteinases-1.
Mentions: Taken together, it is evident that indoxyl sulfate can contribute to renal fibrogenesis via an array of pathophysiological mechanisms (Figure 1), e.g., ROS production, stimulating expression of the profibrotic factor TGF-β, induction of EMT/EPC, promoting cellular senescence and by reducing klotho expression.

Bottom Line: Chronic kidney disease (CKD) is a major global health concern, and the uremic state is highly associated with fibrogenesis in several organs and tissues.Another key feature of CKD is the retention and subsequent accumulation of solutes that are normally cleared by the healthy kidney.The purpose of this brief review is to gather and discuss the current body of evidence linking uremic retention solutes to the fibrotic response during CKD, with a special emphasis on the pathophysiological mechanisms in the kidney.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen , Groningen , Netherlands.

ABSTRACT
Chronic kidney disease (CKD) is a major global health concern, and the uremic state is highly associated with fibrogenesis in several organs and tissues. Fibrosis is characterized by excessive production and deposition of extracellular matrix proteins with a detrimental impact on organ function. Another key feature of CKD is the retention and subsequent accumulation of solutes that are normally cleared by the healthy kidney. Several of these uremic retention solutes, including indoxyl sulfate and p-cresyl sulfate, have been suggested to be CKD-specific triggers for the development and perpetuation of fibrosis. The purpose of this brief review is to gather and discuss the current body of evidence linking uremic retention solutes to the fibrotic response during CKD, with a special emphasis on the pathophysiological mechanisms in the kidney.

No MeSH data available.


Related in: MedlinePlus